Absorption, Tissue Distribution and Elimination of 4-[³H]-Epigallocatechin Gallate in Beagle Dogs

Abstract

Polyphenols found in tea are potent antioxidants and have inhibitory activity against tumorigenicity. The purpose of the described study was to assess the absorption, tissue distribution, and elimination of epigallocatechin gallate (EGCG), the principal catechin found in green tea, in a nonrodent species. 4-[(3)H]-EGCG was administered to beagle dogs by intravenous (IV) and oral routes. Following IV administration of 25 mg/kg, radioactivity in the bloodstream resided predominantly in the plasma. Distribution occurred during the first hour, and the plasma levels of total radioactivity declined with a mean half-life of approximately 7 hours. The apparent volume of distribution (0.65 l/kg) indicated wide distribution, and the total body clearance (1.01 ml/min-kg) was low. A subsequent single oral dose (250 mg/kg) was rapidly absorbed, with peak plasma levels at about 1 hour after administration, followed by elimination with a mean half-life of 8.61 hours. The mean area under the curve (AUC) for total radioactivity was approximately 20% of the value following IV administration (corrected for dose administered). Excretion of radioactivity in the feces predominated over urinary excretion following both IV and oral administration of [(3)H]-EGCG. Tissue distribution was determined 1 hour after an IV dose (25 mg/kg) administered after 27 days of oral treatment with EGCG (250 mg/kg/day) to mimic chronic consumption of tea. Radioactivity was distributed to a variety of epithelial tissues; the highest concentrations were observed in the liver and gastrointestinal tract tissues. Repeat dose oral administration of EGCG resulted in significantly lower blood radioactivity compared to the concentration following a single dose. These results are generally in accord with previous studies in rodents and indicate that, after oral administration, EGCG (as parent compound and metabolites) is widely distributed to tissues where it can exert a chemopreventive effect.

EGCG: Potential application as a protective agent against grass carp reovirus in aquaculture

“…We also used HPLC assay to evaluate the EGCG concentration in grass carp blood and kidney. These data suggest that once‐daily dosing of 150 mg/kg was determined to be the rational choice for controlling GCRV infection in grass carp (Liu, Ge, Wang, Cui, & Han, ; Swezey et al., ; Unno & Takeo, ).…”

ESCO report: Advice on the EFSA guidance document for the safety assessment of botanicals and botanical preparations intended for use as food supplements, based on real case studies

“…The toxicokinetics of radiolabelled EGCG (intravenous, single dose, 25 mg/kg; oral, single dose, 250 mg/kg) have been investigated in beagle dogs (Swezey et al, 2003). This study found that approximately 20% of orally administered EGCG is absorbed systemically in beagle dogs compared with 1.6% (Chen et al, 1997) to 14% (Zhu et al, 2000;Zhu et al, 2001) in rats.…”

Application of Pharmacogenomics to Dietary Cancer Chemoprevention

“…In addition, EGCG can inhibit biochemical markers of tumor initiation and promotion, and thus inhibit the development and growth of cancer. Although low systemic bioavailability is a major obstacle in EGCG administration as reported in animal models Kim et al, 2000;Swezey et al, 2003], the promising health benefits of EGCG have convinced researchers to conduct human intervention studies. Pharmacokinetic research in humans indicates that, after oral administration of EGCG, which has poor gastrointestinal absorption, serum levels of EGCG were found at sub-micromolar or nanomolar ranges Henning et al, 2005], whereas the physiologically relevant serum concentrations of EGCG were at micromolar levels (10-100 M) .…”